Pyrrolidine-Based Organocatalysts for Enantioselective Michael Addition of Cyclohexanone to trans-β-Nitrostyrene

Abstract

A series of readily prepared bifunctional catalysts promote the Michael addition of cyclohexanone to trans-β-nitrostyrene with excellent asymmetric induction. The enantioselection (up to 97%) and diastereoselection (up to 95:5) is comparable to other pyrrolidine­-thiourea organocatalysts recently reported, however, reaction times are often shorter.

addition reactions - asymmetric catalysis - Michael additions­ - bifunctional catalysis - nitroolefin

References

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We also prepared pyrrolidines with 2-carboxamide- or 2-methylacetamide-tethered thiourea and thiouronium functionality. Attempted catalysis of the conjugate addition of cyclohexanone to trans-β-nitrostyrene typically resulted in a syn/anti diastereomeric product ratio of >91:9 with carboxamide-tethered catalysts, comparable to that seen with monofunctional catalysis by (2S)-N-benzylpyrrolidine-2-carboxamide. However, poor syn enantioselectivity (<30% ee) resulted and all methylacetamide-tethered examples demonstrated little or no catalytic activity. Similar amide-linked, amine-thiourea catalysts were also reported to give only the racemic product of ketone addition to nitro-olefins during the course of our study (ref. 7e), presumably as a result of intramolecular hydrogen bonding between thiourea/uronium functionality and the tethering amide.

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